University of Groningen, University Medical Center Groningen, Department of Biomedical Sciences of Cells & Systems, Section of Cognitive Neurosciences.
University of Groningen, University Medical Center Groningen, Department of Biomedical Sciences of Cells & Systems, Section of Cognitive Neurosciences, Groningen.
Curr Opin Psychiatry. 2020 May;33(3):200-205. doi: 10.1097/YCO.0000000000000598.
Recently, it has been questioned whether the re-emergence of psychotic symptoms following antipsychotic discontinuation or dose reduction is attributable to underlying psychotic vulnerability or to rebound effects of chronic use of antipsychotic medication. It was repeatedly shown that relapse rates are high after discontinuation of maintenance treatment. A potential contributing factor could be the increase in density of postsynaptic dopamine D2 receptors in the striatum and the higher affinity of D2 receptors for dopamine after chronic blockade.
To date, little clinical evidence is available for the mechanisms involved in postsynaptic striatal D2 receptor up-regulation after use of antipsychotic medication, and most knowledge comes from animal studies.
Further research is needed to investigate whether antipsychotic medication causes neuroadaptations leading to a dopamine supersensitive state in humans, how long such hypersensitive states may last and what differences exist between high and low D2 affinity antipsychotic drugs. Further, information is needed on discontinuation schedules that provide optimal protection for relapse during hypersensitive periods.
最近,人们质疑抗精神病药停药或减药后出现精神病症状是否归因于潜在的精神病易感性或慢性使用抗精神病药物的反弹效应。反复表明,维持治疗停药后复发率很高。一个潜在的促成因素可能是纹状体中突触后多巴胺 D2 受体的密度增加,以及慢性阻断后 D2 受体对多巴胺的亲和力更高。
迄今为止,关于抗精神病药物使用后纹状体突触后 D2 受体上调涉及的机制,临床证据很少,大多数知识来自动物研究。
需要进一步研究,以调查抗精神病药物是否会导致神经适应,从而导致人类出现多巴胺超敏状态,这种超敏状态可能持续多长时间,以及高亲和力和低亲和力抗精神病药物之间存在哪些差异。此外,还需要了解在超敏期提供最佳保护以防止复发的停药方案。